2-Fluoro-1-cyclopropanecarboxylic acid derivatives are intermediates for preparing pharmaceutical active compounds, in particular antiinfectives from the group consisting of the quinolones (see, eg., Antimicrobial Agents and Chemotherapy 37 (12), 2747 to 2753 (1993) and 38 (3), 611 to 615 (1994) and J. Med. Chem. 37 (20), 3344 to 3352 (1994)).
The reductive replacement of halogen in geminal halogeno-fluorocyclopropane derivatives by hydrogen has already been described in the literature.
One reaction is the method using tri-n-butyl-tin hydride (eg. J. Am. Chem. Soc. 89. 5719 (1967), Tetrahedron Lett. 1967, 1123, J. Org. Chem. 35, 33 (1970) and Synthesis 1970, 499). The use of tri-n-butyl-tin hydride is scarcely expedient, economically and ecologically, owing to its toxicity, its poor accessibility, which gives rise to high costs, and the large amount required.
Another method is the reaction using sodium in liquid ammonia (see, eg., Chem. Ber. 104, 1921 (1971)). This process also has the disadvantage that it is highly complex in the case of an industrial procedure.
In a further process, the dehalogenation is carried out using other metals, preferably Raney nickel, in the presence of hydrogen and a base (see, eg., J. Fluorine Chem. 49, 127 (1990) and WO 95/04712). Bull. Chem. Soc. Jap. 45, 1926 (1972) describes that, in the hydrogenolytic dehalogenation of 7-chloro-7-fluorobicyclo[4.1.0]heptane with Raney nickel, the desired product, 7-fluorobicyclo[4.1.0]heptane, was only obtained using 1,2-diaminoethane as base, and no reaction took place using other bases.
This process has the disadvantage that the selectivity is low. The selectivity can be increased if low temperature (eg. room temperature) is employed. However, this leads to incomplete conversion and to reaction times of 50 hours and more. Even when a large excess of Raney nickel and base are used, the conversion rate can only be increased slightly and the reaction time can only be shortened slightly. Thus, in the last-cited literature reference, when 852 mol % of Raney nickel and 6000% of 1,2-diaminoethane (each based on the starting material) are used, a conversion rate of only 58% is achieved in 24 hours at 18 to 22.degree. C. According to WO 95/04712 also, large excesses of Raney nickel and 1,2-diaminoethane are used, more precisely 466 to 3785 mol % of Raney nickel and 300 to 1000 mol % of 1,2-diaminoethane.
However, it is essential that the highest possible conversion rate is achieved, since it is not possible to separate the desired products, in particular the cis isomers, from the starting materials by distillation with reasonable expenditure.
Although the reaction proceeds considerably faster if the reaction temperature is elevated, in which case the required amounts of Raney nickel and 1,2-diaminoethane can also be reduced, at the same time the selectivity greatly decreases. Thus, at 80.degree. C., a yield of only 10% of theory is achieved (see J. Fluorine Chem. 49, 127 (1990)).
There is therefore still the requirement for a process which gives the desired product in good yields and selectivities in a short reaction time and with small amounts of metals and bases used.